Fig. 1
From: Structural and functional specificity of H3K36 methylation
Set2/SETD2 is generally conserved among fungi and metazoans. A Multiple sequence alignment (MSA) of Set2 homologs across fungi and metazoan species. MEGAX software and NCBI MSA viewer 1.13.1 [230] were used to generate an alignment of the primary amino acid sequences of Set2/SETD2 homologs from fission yeast, budding yeast, fungi Aspergillus turcosus, and metazoan species including human, rat, mouse, zebrafish, fruitfly, and nematode worm C. elegans. 35% of the human SETD2 amino acid sequence is conserved in fission yeast Set2 , even for sequences beyond the catalytic SET domain. 53% of the amino sequence in the catalytic SET and post-SET domains is identical in fission yeast Set2 and human SETD2. Residues that are generally conserved across species are indicated in red. Residues that are identical or similar in polarity across species are, respectively, highlighted in black or grey. Conserved “decision-making” residues that regulate the degree of methylation are circled in blue. Non-conserved aromatic residues that make contact with histone tails and possibly participate in methylation regulation are circled in red. Domain structure of fission yeast Set2 and human SETD2 are also shown to indicate the relative amino acid positions of the MSA sequences in the SETD2 homologues. B Conserved motifs in human SETD2 SET-domain. i Surface representation: sections of conserved motifs are highlighted (green, teal, cyan, and orange). Pymol visualization is derived from the crystallized structure database in the Protein Data Bank, entry 5V21 [74]. ii Projection of the conserved sequence of yeast Set2 and human SETD2. The SET domain crystalized structure highlights (1) a regulatory LIN loop, (2) a triangular core motif separated from the catalytic site, and (3) histone-interacting residues (refer Figs. 3 and 4). Conserved residues in the triple β-sheet in the triangular core of the SETD2 SET domain (green) endow the SET domain with its recognizable triangular shape, which maintains the structure of the domain. Conserved LIN-loop (teal, cyan and orange) and α8 (short, white α-helix region) in the closed conformation secure the histone tail in position for methylation.